Effects of sub-chronic exposure to atmospheric PM2.5 on fibrosis, inflammation, endoplasmic reticulum stress and apoptosis in the livers of rats
Effects of sub-chronic exposure to atmospheric PM2.5 on fibrosis, inflammation, endoplasmic reticulum stress and apoptosis in the livers of rats
复制标题
大气PM2.5亚慢性暴露对大鼠肝脏纤维化、炎症、内质网应激和细胞凋亡的影响
DOI：
10.1039/c7tx00262a
复制
发表时间：
2018-03-01
影响因子：
2.1
通讯作者：
Cai, Zongwei
中科院分区：
文献类型：
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作者：
Li, Ruijin;Zhang, Mei;Cai, Zongwei
流行病学研究表明，接触PM2.5与肝癌有关。然而，PM2.5的肝毒性和相关分子机制尚未得到充分的描述。在此，我们报告了我们对中国太原夏季和冬季暴露于PM2.5的大鼠肝脏纤维化，炎症，内质网（ER）应激和细胞凋亡的调查。雄性SD大鼠每3天气管内灌注1次，连续60天亚慢性暴露PM2.5（夏季：0.2、0.6、15 mg / kg体重；冬季：0.3、1.5、2.7 mg / kg体重）。结果表明，高剂量PM2.5暴露可引起：(1)肝脏组织病理改变，肝脏功能下降，主要表现为AST、ALT、CYP450和GST活性升高；(2)引发肝纤维化，tgf - β 1、Col I、Col III和MMP13 mRNA和蛋白表达显著上调，与对照组相比，tnf - α、IL-6和HO-1过表达，炎症增强；(3)通过激活GRP78/ATF6/CHOP/TRB3/caspase 12通路诱导肝脏内质网应激和细胞凋亡。数据还表明，太原市冬季PM2.5所致肝损伤较夏季PM2.5所致肝损伤更为严重。这项工作为PM2.5诱导肝损伤的机制提供了新的见解，并有助于理解PM2.5可能影响肝脏疾病的潜在机制。
Epidemiological studies have revealed that exposure to PM2.5 is linked to liver cancer. However, the hepatic toxicity and relevant molecular mechanisms of PM2.5 have not yet been fully described. Herein, we report on our investigation of the fibrosis, inflammation, endoplasmic reticulum (ER) stress and apoptosis in the livers of rats, caused by exposure to PM2.5 during summer and winter in Taiyuan, China. Male SD rats were sub-chronically exposed to PM2.5 (in summer: 0.2, 0.6, 15 mg per kg of b.w.; in winter: 0.3, 1.5, 2.7 mg per kg of b.w.) via intratracheal instillation once every 3 days for 60 days. The results showed that exposure to high dosages of PM2.5 caused the following: (1) hepatic histopathological changes and liver function decline through elevating the activities of AST, ALT, CYP450 and GST; (2) triggered liver fibrosis, in which TGF-beta 1, Col I, Col III, and MMP13 mRNA and protein expression were significantly upregulated, and enhanced inflammation with the overexpression of TNF-alpha, IL-6 and HO-1 versus the control; (3) induced liver ER stress and cell apoptosis via activating the GRP78/ATF6/CHOP/TRB3/caspase 12 pathway. The data also indicated that the liver injury induced by winter PM2.5 in Taiyuan was more serious compared to that induced by summer PM2.5. This work provides new insight into the mechanisms of PM2.5-induced liver injury, and aids the understanding of the underlying mechanisms by which PM2.5 might affect liver diseases.